The residents of the study area, approximately 8000 people aged at least 5 years, have participated in a longitudinal population study since 1965, allowing study of the risk factors and effects of diabetes mellitus. Risk factors for obesity, hypertension, and nephropathy are also studied, along with the relationships of these diseases to diabetes and their effects on development of vascular complications and mortality. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. The roles of obesity, serum insulin concentrations, impaired glucose regulation, occupational and leisure-time physical activity and diabetes in relatives are assessed. Findings on risk factors for diabetes are applied to a multicenter randomized clinical trial of prevention of type 2 diabetes that is currently in a long-term outcomes phase (the Diabetes Prevention Program Outcomes Study). Studies of the genetics of type 2 diabetes, obesity, and diabetes complications are described in other projects.[unreadable] [unreadable] [unreadable] Knowledge of diabetes risk factors coming from this and other studies led to the hypothesis that type 2 diabetes could be prevented or delayed in adults at high short-term risk. This hypothesis was confirmed in the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial in which many of the participants and investigators in this project participated. We are now in a long-term follow-up phase, the Diabetes Prevention Program Outcomes Study (DPPOS), to assess long-term success with weight loss, reduction in the incidence of diabetes, and effects on diabetes complications. The DPPOS also began a genetics component to test whether genes with known or suspected effects on type 2 diabetes affected diabetes incidence in the DPP and interacted with study interventions.